title: Reactive oxygen species are related to ionic fluxes and volume decrease in apoptotic cerebellar granule neurons: role of NOX enzymes.
abstract: Reactive oxygen species (ROS) are produced early during apoptosis of cerebellar granule neurons induced by low potassium (K5) and staurosporine (Sts). In addition, K5 and Sts activate NADPH oxidases (NOX). Recently, we described that K5 and Sts induce apoptotic volume decrease (AVD) at a time when ROS generation and NOX activity occur. In the present study, we evaluated the relationship between ROS generation and ionic fluxes during AVD. Here, we showed that K5- and Sts-induced AVD was inhibited by antioxidants and that direct ROS production induced AVD. Moreover, NOX inhibitors eliminated AVD induced by both K5 and Sts. Sts, but not K5, failed to induce AVD in cerebellar granule neurons from NOX2 knockout mice. These findings suggest that K5- and Sts-induced AVD is largely mediated by ROS produced by NOX. On the other hand, we also found that the blockage of ionic fluxes involved in AVD inhibited both ROS generation and NOX activity. These findings suggest that ROS generation and NOX activity are involved in ionic fluxes activation, which in turn could maintain ROS generation by activating NOX, leading to a self-amplifying cycle.
authors.affiliation: División de Neurociencias, Departamento de Neurodesarrollo y Fisiología, Universidad Nacional Autónoma de México, México, DF, México.
authors.forename: Berenice
authors.initials: B
authors.lastname: Hernández-Enríquez
authors.forename: Alicia
authors.initials: A
authors.lastname: Guemez-Gamboa
authors.forename: Julio
authors.initials: J
authors.lastname: Morán
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D048429:Cell Size; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007473:Ion Channels; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; D019311:Staurosporine; D011188:Potassium